Non-canonical Wnt signaling and lymphostromal interactions: the role of Wnt4/Frizzled6 axis in early immune development

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All cells of the adult immune system are derived from a small number of bone marrow hematopoietic stem cells (HSC) that are found in specialized pockets or niches, surrounded by other cells that are believed to regulate HSC function. In addition to being able to develop into the different blood cell lineages, HSC also have the unique ability to self-renew. Their infrequent cell divisions are asymmetrical, resulting in the generation of one daughter HSC, identical to the mother cell, and one progenitor cell that has lost several stem cell characteristics. This self-renewal is dependent on HSC-niche interactions and is essential for the continuous generation of circulating blood cells. One of the greatest technical challenges in the field is to develop methods for HSC expansion in culture while limiting the loss of their self-renewal capacity.